The Relationship Between LPO^BDNF Neurons Mediated Thermoregulation And Reanimation From General Anesthesia

Objective:The application of general anesthetic drugs has facilitated most surgical procedures and greatly improved patient comfort and safety.The reversible loss of consciousness is a characteristic effect of general anesthetics,which is believed to be related to the neural circuit that regulates sleep-wakefulness.In addition,a decrease in body temperature occurs during general anesthesia.The lateral preoptic area（LPO）is an important brain area involved in the regulation of sleep and cooling;and has been reported to regulate the process of anesthesia and wakefulness,but the exact mechanism of regulation remains unclear.This experiment was conducted to investigate how LPO thermoregulatory neurons are involved in general anesthesia,understand the interplay between thermoregulation and anesthesia,and investigate whether thermoregulatory neurons affect general anesthesia.Methods:1)Isoflurane,an anesthetic gas whose drug metabolism is less affected by hemodynamics,was chosen as the vehicle for this experiment;2)A high-precision temperature recorder was embedded in the abdominal cavity of wild-type mice to record the physiological temperature fluctuations of mice,and a time period with stable and consistent body temperature was selected for the experiment;3)Observe the association between body temperature at the end of anesthesia and the time of recovery of righting reflex（RORR）in wild-type mice at different ambient temperatures;4)Specifically activate LPO neurons in wild-type mice using chemicalgenetics technology,and to initially investigate the association between cooling and the RORR time after activation of LPO;5)Specifically activate or inhibit LPO^BDNF neurons,observe the changes in body temperature of mice in the awake or anesthetized state at 16℃and 32℃to deter mine the temperature regulation range of the subsequent experimental environment;6)Observe the effects of activating or inhibiting LPO^BDNF neurons on the RORR time in survival appropriate temperatures（18℃,21℃,25℃,29℃）and thermoneutral temperatures（32℃）;7)Control the ambient temperature（18℃or 32℃）during general anesthesia by circulating water bath device and monitor the body temperature before and after anesthesia as well as the prefrontal cortex EEG activity;8)Fiber optic fluorescence detector to monitor the dynamic changes of LPO^BDNF neuronal activity during anesthesia.Results:1)Body temperature at the end of anesthesia in wild-type mice was significantly correlated with RORR time;2)Body temperature of mice before and after anesthesia decreased significantly and the RORR time was prolonged by extensive activation of LPO neurons;3)Both heat production and heat dissipation capacity of mice decreased during anesthesia;mice showed severe hypothermia when anesthesia was performed at 16℃;mice could maintain a body temperature above 35℃when anesthesia was performed at 32℃;4)When the ambient temperature was lower than 29℃,activation of mouse LPO^BDNFneurons significantly prolonged the RORR time;when it was higher than 29℃,activation of mice LPO^BDNF neurons did not affect the RORR time;5)In mice with activated LPO^BDNF neurons and significant hypothermia,the initial sedation level of anesthesia decreased while the sedation level end of anesthesia increased;6)LPO^BDNF neuron activity showed a jittery decrease at the beginning of anesthesia and a jittery increase at the end of anesthesia.Conclusions:LPO^BDNF neurons deepen the depth of anesthesia and prolong the awakening time by lowering body temperature;Hypothermia deepens the depth of general anesthesia;LPO^BDNF neurons may be involved in reanimation from general anesthesia.